Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117

Jelena Lazic; Sanja Skaro Bogojevic; Sandra Vojnovic; Ivana Aleksić; Dusan Milivojevic; Martin Kretzschmar; Tanja Gulder; Milos Petkovic; Jasmina Nikodinovic-Runic

doi:10.3390/molecules27123729

journal article Open Access Jun 09, 2022

Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117

Jelena Lazic

Sanja Skaro Bogojevic

Sandra Vojnovic Ivana Aleksić Dusan Milivojevic Martin Kretzschmar

Tanja Gulder

Milos Petkovic Jasmina Nikodinovic-Runic

Molecules Vol. 27 No. 12 pp. 3729 · MDPI AG

View at Publisher Save 10.3390/molecules27123729

Abstract

Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62–17.00 µg/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditiselegans at concentrations up to 50 µg/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 µg/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br2, respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski’s “rule of five”, with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.

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Details

Published: Jun 09, 2022
Vol/Issue: 27(12)
Pages: 3729
License: View

Authors

J

Jelena Lazic

Graduate School, University of Nova Gorica, SI-5000 Nova Gorica, Slovenia; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia

S

Sanja Skaro Bogojevic

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia

S

Sandra Vojnovic

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia

I

Ivana Aleksić

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia

D

Dusan Milivojevic

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia

M

Martin Kretzschmar

Institute of Organic Chemistry, Leipzig University, 04103 Leipzig, Germany

T

Tanja Gulder

Institute of Organic Chemistry, Leipzig University, 04103 Leipzig, Germany

M

Milos Petkovic

Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia

J

Jasmina Nikodinovic-Runic

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia

Funding

the Science Fund of the Republic of Serbia, IDEJE Award: 451-03-68/2022-14/200042

BioECOLogics Award: 451-03-68/2022-14/200042

Deutscher Akademischer Austauschdienst e.V. (DAAD) Award: 451-03-68/2022-14/200042

Emmy-Noether program of the German Research Foundation Award: 451-03-68/2022-14/200042

Cite This Article

Jelena Lazic, Sanja Skaro Bogojevic, Sandra Vojnovic, et al. (2022). Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117. Molecules, 27(12), 3729. https://doi.org/10.3390/molecules27123729

Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117

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